The present invention is drawn to an apparatus and method for analyzing particle size in a dense suspension using a single fiber optical probe with a light spectrometer.
In situ measurement of particle size in turbid media has many applications in medicine and in the pharmacology industry. Many diseases are correlated with the morphological alterations of cells, which are used for diagnosis in pathology. An inexpensive, non-invasive, in-vivo technique to detect alterations of scatterer size in tissue would improve patient care and reduce medical cost.
Known methods of measuring particle-size in dense suspensions include frequency-domain photon migration and other photon diffusion based techniques that measure the wavelength dependence of the reduced scattering coefficient. An average effective scatterer size can be determined from a simple parameterization of the wavelength dependence of xcexcsxe2x80x2(xcex). Alternatively, the size distribution and volume ratio of particles can be calculated from xcexcsxe2x80x2(xcex) using an inversion method. The disadvantage of photon diffusion based techniques is that the volume sampled must be large enough for the diffusion approximation to hold, i.e.xcx9c1 cm3 or larger. A smaller volume is probed, xcx9c3 mm3, when variations in the pattern of polarized light back-scattered from a turbid media are used to estimate scatter size. However, this method does not provide information on the scatterer size distribution width. Backman et al. have recently reported using polarized diffuse reflectance spectroscopy to determine scatterer size distributions. V. Backman et al., xe2x80x9cPolarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,xe2x80x9d IEEE J. Sel. Top. Q. Electronics, vol. 5, pp. 1019-26, (1999). Scatterer size distributions can be determined from non-polarized wavelength dependent diffuse reflectance measurements when the measurement wavelength is much less than the scatterer diameter. Additional methods of particle size distribution determination based on the anomalous diffraction approximation are currently being developed.
From the foregoing, it will be appreciated that there is a need in the art for an inexpensive, in situ technique to detect alterations of scatterer size in tissue, turbid, or dense media.
The present invention is drawn to an in situ technique to determine scatterer size by measuring the white light elastic scattering spectroscopy (ESS) signal with a single-fiber, optical probe. The single-fiber, optical probe is optically coupled to a light source and optically coupled to a spectrometer. In this way, the probe serves to introduce light into the sample and to collect light scattered by the sample. The collected light is transmitted to the spectrometer. An elastic scatter signal (ESS) spectrum of the sample is measured and analyzed to determine the scatterer particle size. The particle size analysis method may include compensating for the refractive index and/or light absorption of the sample medium.
It has been observed that different size particles have distinct oscillation patterns in an ESS spectrum. Furthermore, the frequency of oscillations increases with particle size, and the particle size is approximately a linear function of the total number of oscillations. Derivatives of the spectra with respect to wavelength make the oscillation pattern easier to count. Thus, particle size is related to the number of oscillations in a given wavelength range. The spectra wavelength may range from 100 to 900 nm, more preferably from 450 to 800 nm.
The use of a single fiber probe of small diameter has several advantages. A fairly small volume is probed allowing for local measurement of particle size. Secondly, the probe can easily fit and into small compartments in an industrial setting and down endoscope channels for performing tissue spectroscopy. The experimental setup incorporating the fiber optic probe is simple and inexpensive, requiring only one steady-state visible-NIR spectrometer.